title: Evaluation of IgA deficiency in Sardinians indicates a susceptibility gene is encoded within the HLA class III region.
abstract: IgA deficiency (IgA-D) has been associated with the HLA region, in particular with the North European haplotype HLA-A1, -B8, -DR3, but the exact location of the susceptibility gene(s) is unknown. Some reports suggest that a susceptibility gene is encoded in the class II region, while others implicate the class III region. We exploited differences between the common Sardinian and North European HLA-DR3 haplotypes to help localize the IgA-D susceptibility gene(s). With the knowledge that approximately 13% of HLA-DR3 homozygous individuals of North European origin are IgA-D, we examined 43 HLA-DR3 homozygous Sardinians to find that all had normal serum IgA, IgG and IgM levels. A detailed analysis of their MHC haplotypes indicated a common Sardinian HLA-DR3 haplotype TAP1A, TAP2A, HLA-DQB1*0201, -DQA1*0501, -DRB1*0301, LH1-(Z + 2), D3A-(Z + 2), C4B-0, C4A-L, G11-15, Bf-0-4, C2-a, HSP70-7.5, 9N3-(Z + 10), 82I-(Z - 2), TNFalpha-9, 62-(Z - 20), HLA-B18, -Cw5, -A30 which diverges from the common North European HLA-DR3 haplotype telomeric to the HLA-DR region. In parallel studies of five Sardinians with IgA-D, two of the 10 HLA haplotypes (20%) contained HLA-DR3, a frequency similar to that observed in the background population. One of these was the HLA-DR3- B8 North European haplotype, which occurs rarely in Sardinia. Our data favour the hypothesis that a class III region allele, present on the common North European but not on the Sardinian HLA-DR3 haplotype, confers susceptibility to IgA-D.
authors.affiliation: Divisione Pediatrica, Ospedale S. Michele, Cagliari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cucca
authors.forename: Z B
authors.initials: ZB
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Khanna
authors.forename: F
authors.initials: F
authors.lastname: Cossu
authors.forename: M
authors.initials: M
authors.lastname: Congia
authors.forename: M
authors.initials: M
authors.lastname: Badiali
authors.forename: R
authors.initials: R
authors.lastname: Lampis
authors.forename: F
authors.initials: F
authors.lastname: Frau
authors.forename: S
authors.initials: S
authors.lastname: De Virgiliis
authors.forename: A
authors.initials: A
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Arnone
authors.forename: P
authors.initials: P
authors.lastname: Piras
authors.forename: R D
authors.initials: RD
authors.lastname: Campbell
authors.forename: M D
authors.initials: MD
authors.lastname: Cooper
authors.forename: J E
authors.initials: JE
authors.lastname: Volanakis
authors.forename: S H
authors.initials: SH
authors.lastname: Powis
mesh_terms: D004198:Disease Susceptibility; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D017098:IgA Deficiency / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D007558:Italy / Q000453:epidemiology
chemical_list: D015803:HLA-DR3 Antigen